Biomarker–Imaging Dissociation in Wild-Type Cardiac Amyloidosis after Treatment with Patisiran

Introduction

Amyloidosis is a progressive and complex disease caused by the extracellular deposition of insoluble fibrillar proteins in organs and tissues. Among the different types of amyloidosis, cardiac amyloidosis poses unique challenges due to its direct impact on cardiac function, structure, and electrical conduction. This condition can lead to restrictive cardiomyopathy, resulting in heart failure, arrhythmias, and other potentially life-threatening complications. Transthyretin amyloidosis (ATTR) is one of the more common forms of cardiac amyloidosis, occurring in both hereditary and non-hereditary forms. The hereditary form is caused by genetic mutations, whereas the non-hereditary form, known as wild-type transthyretin amyloidosis (ATTRwt), predominantly affects older adults and does not involve genetic mutations.

Recent therapeutic advances in the treatment of amyloidosis, particularly cardiac ATTRwt, have opened promising avenues for reducing amyloid burden in affected patients. Patisiran, an RNA interference (RNAi)-based therapy, targets the hepatic synthesis of transthyretin, thereby lowering circulating transthyretin protein levels available to form amyloid deposits in tissues. This mechanism represents a major advance because it directly reduces the source of the pathology rather than merely managing symptoms.

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